The major objective of the Mouse Core is to provide a centralized service oriented facility to insure the capacity of each participating project lab to produce and maintain transgenic and gene-disrupted mice. The facility was developed in 1995 within the Pulmonary Division. Initially, the facility was equipped using funds from the Barnes-Jewish Hospital Foundation, and has historically primarily served labs involved in pulmonary research. More recently, the facility has been supported largely by two NIH grants, including a SCOR grant on asthma (Mechanisms of Airway Inflammation and Remodeling, P50 HL56419, Michael J. Holtzman, PI), and a Program Project Grant (Mechanisms in the Remodeling of Lung Structure, P01 HL29594, Robert M. Senior, PI). As most of the projects in this application propose genetic experiments in mice, we propose that this grant also support a proportional part of the Mouse Core. Many of the Project Leaders, Co-Investigators, and Core Leaders on this application (Holtzman, Mecham, Pierce, Senior, Walter, Urban, Atkinson, Brody, Shipley) have been utilizing it for several years for work related to these two grants as well as other projects. Since 1995, the facility has generated more than 100 lines of transgenic and gene-targeted mice, with multiple founders or chimeras of each line in most cases. This has resulted in an economy of scales by minimizing overhead and avoiding duplication of a highly technical skill requiring specialized equipment and animal facilities. The Mouse Core is a major avenue for collaborations. The ability to perform gain of function and loss of function experiments in vivo has and will enhance our understanding of the molecular mechanisms governing remodeling of the lung in COPD. Additionally, the core has served to help develop a murine model of cigarette smoke-induced pulmonary emphysema. In this application, the core will also support the infrastructure of this model, as it will be heavily utilized by most Project Leaders in the program. The core is fully equipped to provide both transgenic/knockout as well as cigarette smoking services, and utilizes dedicated space within our state of the art animal facility to fulfill these functions. In addition, the Mouse Core will support the infrastructure surrounding use of the BUXCO system for making invasive resistance and compliance measurements. These studies will be overseen by Dr. Michael J. Holtzman and will be done by Ms. Suzanne Swanson, a research techinican who has considerable expertise using this system.